Karzon D T, Bolognesi D P, Koff W C
Department of Pediatrics, Vanderbilt Medical School, Nashville, TN 37232.
Vaccine. 1992;10(14):1039-52. doi: 10.1016/0264-410x(92)90114-y.
The pathogenesis and clinical expression of HIV-1 infection in humans is considered in terms of classical pathogenetic studies of viral infections for which successful vaccines have been produced. The unique features of HIV pathogenesis are defined, and gaps in knowledge identified as a framework for considering designs for immune intervention. Envelope-derived candidate vaccines have been used in immunization and challenge experiments in SIV/macaque or HIV/chimpanzee models, presented either as vaccinia recombinant vectors or as subunits, singly or in sequence. These studies have been paralleled by clinical trials for safety and immunogenicity in seronegative individuals. Data generated will permit comparison of immune responses to specific antigens and delivery systems in animal models and in humans. In limited studies conducted under optimized conditions, non-human primates have been protected against virus challenge when immunized with some candidate vaccines or following passive transfer of high-titred antibody. Consideration of current information suggests that in order to prevent HIV infection it may be necessary to devise new strategies capable of inducing and maintaining high threshold titres of biologically relevant antibody as well as persistence of active cytotoxic T cells recognizing multiple epitopes.
根据已成功研发出疫苗的病毒感染的经典发病机制研究，来探讨人类HIV-1感染的发病机制和临床表现。明确了HIV发病机制的独特特征，并确定了知识空白，以此作为考虑免疫干预设计的框架。包膜衍生候选疫苗已用于SIV/猕猴或HIV/黑猩猩模型的免疫和攻毒实验，呈现形式为痘苗重组载体或亚单位，单独使用或按顺序使用。这些研究同时还伴有针对血清阴性个体的安全性和免疫原性的临床试验。所产生的数据将有助于比较动物模型和人类对特定抗原及递送系统的免疫反应。在优化条件下进行的有限研究中，用一些候选疫苗免疫或进行高滴度抗体被动转移后，非人灵长类动物可免受病毒攻击。对当前信息的思考表明，为预防HIV感染，可能有必要设计新策略，以诱导并维持高阈值滴度的生物学相关抗体，并使识别多个表位的活性细胞毒性T细胞持续存在。
